Research

Background

Cerebrovascular accidents (i.e. strokes) with an annual incidence of 13.7 million people are the second leading cause of death and disability worldwide. A large part of cerebrovascular events are caused by the rupture of carotid artery plaques. To prevent (recurrent) ischemic strokes a carotid endarterectomy (CEA) is performed. Clinical risk stratification in these patients is mainly based on the stenosis degree (geometry, maximum blood velocity) caused by the atherosclerotic plaque and clinical risk factors, such as hypertension and hyperlipidemia. However, this risk stratification is rather suboptimal since there is more and more evidence that, regardless of stenosis degree, plaques containing a lipid-rich core covered by a thin fibrous cap (vulnerable plaques) are more prone to rupture than plaques mainly containing fibrous tissue (stable plaques). Therefore, other parameters are needed to identify vulnerable plaques and, with that, improve (individual) clinical care.

What has been done
In vascular ultrasound, research interest has shifted from stenosis degree to plaque composition, geometry, and deformation. Since lipids are softer than fibrous tissue, it can be expected that vulnerable plaques deform more than fibrous plaques in response to the pulsating blood. Over the past years we developed different two-dimensional techniques, called compound ultrasound strain imaging and shear wave elastography to characterize tissues non-invasively. With these methods it could be possible to determine elastic properties of carotid plaques in order to identify the vulnerable ones. Since blood flow is representative for the function of the arteries and is also an important predictor for the risk of developing plaques, techniques to study the blood velocity are already available in commercial ultrasound machines. However, these techniques are based on the Doppler principle, which implies that only the velocity component parallel to the ultrasound direction can be estimated. Thus, true blood velocity vector and complex blood flow phenomena often present in our cardiovascular system and true blood flow vectors cannot be captured. To accurately estimate the blood velocity in the carotid artery we are developing ultrafast flow techniques.

Our research aim
Our current research aims are:

• to further develop and validate the 2D techniques (i.e. strain and shear wave elastography, and ultrafast flow) in patients with atherosclerotic diseases and show the relation between measured values and cardiovascular events in order to establish new prognostic markers.
• to extend the already developed 2D technique to a 3D technique to be able to localize the most vulnerable part of a plaque, if present, in 3D.

Methods

In- and ex-vivo clinical studies are being performed in order to validate the in patient performance of the developed 2D technique in patients and to link the strain, shear wave, and flow measures to the cardiovascular risk profile of patients. To circumvent the angular dependence of conventional Doppler-based blood flow imaging techniques, the velocity vector is estimated by 2D (speckle) tracking. However, this technique requires high frame rates. To achieve this, plane wave transmission (one transmission over an entire region instead of multiple focussed ultrasound pulses) with displacement compounding is used to measure with a high frame rate and sufficient image quality. The 2D techniques are extended to 3D by using ultrafast ultrasound transmission sequences.

Results

A first in vivo validation study of compound strain imaging showed that the technique allowed successful differentiation between plaques with a large lipid pool and fibrous plaques with a sensitivity, specificity, positive and negative predictive value of 85%, 71%, 81% and 77%, respectively (Hansen, 2016) . It has been shown that using the flow techniques complex flow patterns could be visualized in healthy and diseased carotid arteries and quantified using a vector complexity measure that increased with increasing wall irregularity (Saris, 2019).

Temporal evolution of the velocity vector fields in the carotid artery of a patient after endarterectomy and patch placement. From: Saris et al. 2019

First in vivo application of 3D strain measurements showed distensibility values matched with previously published values, while the corresponding volumetric principal strain maps revealed locally elevated compressive and tensile strains (Fekkes, 2019).

Funding

• Characterization of atherosclerotic plaques in the carotid artery using non-invasive ultrasound elastography (VIDI grant of the Netherlands Organisation for Scientific Research NWO and the Dutch Technology Foundation STW and Philips Medical Systems, finished)

• Ultrafast imaging, the next level of cardiovascular diagnosis (VICI grant of the Netherlands Organisation for Scientific Research NWO and the Dutch Technology Foundation STW, finished)

• ULTRA-X-TREME: Ultrafast Ultrasound Imaging for Extended Diagnosis and Treatment of Vascular Disease (NWO Perspectief grant, active).

• Ultra-COMPASS: Ultrafast ultrasonic compound push wave imaging and strain estimation for personalized stroke risk stratification (Radboud Institute of Health Sciences Junior researcher project 2019, Radboudumc, active)

• VORTECS: Ultrafast ultrasound blood flow quantification for diagnosis and treatment of vascular diseases ('Connecting Innovators', Open Technology Program of the Netherlands Organization for Scientific Research (NWO), 2019, active).

• Regional Research Project 2020, Radboudumc-Rijnstate Initiative